1. Field of the Invention
This invention relates to a carcinostatic containing a compound having an activity to inhibit the function of an oncogene as an effective component. More specifically, this invention is directed to a carcinostatic agent which is capable of inhibiting the function of ras and src oncogenes through inhibition of the function of the oncogene products thereof. This invention also relates to a method for inhibiting such oncogene function and a method for normalizing cell morphology and growth habits of cancer cells. Furthermore, this invention relates to a method for treating a cancer of a mammal. This invention involves use of a compound extracted from Ervatamia microphylla.
2. Prior Art
Oncogenes play important roles in the initiation and promotion of cancers. An oncogenes is generated by conversion of a protooncogene on a genome DNA of a normal cell through various abnormalities such as point mutation, translocation, and amplification. Of the more than 70 oncogenes that have so far been found, ras oncogenes are some of the most popular oncogenes, and are said to be found in about 20% of human tissues of colon cancer, breast cancer, leukemia, and the like. In view of such situation, substances that are capable of inhibiting the action of the ras and other oncogenes, namely, that are capable of inhibiting the function of the product of ras and other oncogenes is highly awaited as a new series of therapeutic agents. The presently known substances that are capable of inhibiting the action of the ras oncogene product, namely, Ras protein include oxanosin isolated from Actynomyces (N. Shimada et al., The Journal of Antibiotics 34, 1216-1218, 1981) and compactin isolated from a mold (O. Ito et al., Cancer Research 49, 996-1000, 1989).
Such known substances capable of inhibiting the action of the ras oncogene products, however, suffer from low stability and high toxicity, and none are clinically applicable. Development of a new medicament that is clinically applicable, and that has an inhibitory mechanism different from such known oncogene inhibitors is highly demanded.
In order to find an oncogene inhibitory substance of clinical utility, the inventors of the present invention have conducted a screening of substances of plant origin in search for a substance that is capable of inhibiting the action of ras and other oncogenes by using normalization of cell morphology and growth habits for the index, and consequently, found that such an activity is present in an extract of leaves of a tropical plant, Ervatamia microphylla Kerr. The inventors of the present invention then succeeded in the isolation and characterization of the active component in the extract. The present invention has been completed on the bases of such study.